The Developmental Genomics Section has been using a combination of zebrafish genetics and molecular embryology to study ear and hearing development. We have focused our attention on the study of several lines isolated in a screen for embryonically lethal mutations in zebrafish. Three of these mutations are being actively studied. The first is a mutation in the forkhead related transcription factor Foxi1. This mutation has defects in both otic placode formation and jaw development. We are studying the mechanism of function for this transcription factor and are beginning to create a connection between sensory placode development and the formation of craniofacial elements. A second mutation is in the zebrafish ortholog of the mouse gene Oct4. This gene is essential for maintaining stem cell pluripotency. We are performing transcriptional profiling in mouse ES cells and zebrafish embryos after modulating Oct4 levels. The third mutation affects the regenerative ability in several tissues of the zebrafish embryo including the hair cells of the inner ear. We are actively analyzing this mutation for its role in renewable cell populations. Another focus of the lab is to develop tools for studying gene expression on a genome wide scale. We have developed a technique for rapidly mapping the integration sites for retroviruses and transposable elements and used that technique to define the global genomic profiles for MLV, HIV-1, and Sleeping Beauty based vectors. We are now in the process of mapping thousands of proviral integrations in the zebrafish germline to create an archived zebrafish mutant resource.